8-(3-氯苯基)-1,4-二氧杂-螺[4.5]癸烷-8-甲腈 | 65619-33-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 8-(3-氯苯基)-1,4-二氧杂-螺[4.5]癸烷-8-甲腈
• 英文名称: 8-(3-chlorophenyl)-1,4-dioxa-spiro[4.5]decane-8-carbonitrile
• 英文别名: 8-(3-chlorophenyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile
• CAS: 65619-33-2
• 化学式: C₁₅H₁₆ClNO₂
• 分子量: 277.751
• InChiKey: SGEYGEOBLZEULG-UHFFFAOYSA-N

物化性质

• 熔点：
  68-71 °C
• 沸点：
  444.6±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-(3-氯苯基)-1,4-二氧杂-螺[4.5]癸烷-8-甲腈 在 sodium hydroxide 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇 为溶剂， 反应 36.0h， 生成 8-(3-chlorophenyl)-N,N-dimethyl-1,4-dioxaspiro[4.5]decan-8-amine
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014
• 作为产物：
  描述：

  2-Carbomethoxy-4-(m-chlorphenyl)-4-cyano-cyclohexanon 在 硫酸 、 对甲苯磺酸 作用下， 以 溶剂黄146 、 苯 为溶剂， 反应 30.0h， 生成 8-(3-氯苯基)-1,4-二氧杂-螺[4.5]癸烷-8-甲腈
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014

文献信息

• ORGANIC COMPOUNDS
  申请人：Bäschlin Daniel Kaspar

  公开号：US20130012485A1

  公开（公告）日：2013-01-10

  Compounds of the formula (I) are provided: wherein V, W, X, Y, Z, R 3 , R 4 , R 5 , R 6 , R 7 and m are as defined in the specification; and pharmaceutically acceptable salts and prodrugs thereof. The compounds may be useful in the treatment or prevention of various diseases and conditions in which dipeptidylpeptidase-IV (DPP-IV) is implicated.

  提供了化学式（I）的化合物： 其中V、W、X、Y、Z、R3、R4、R5、R6、R7和m的定义如规范中所述；以及其药学上可接受的盐和前药。这些化合物可能在治疗或预防各种与二肽基肽酶-IV（DPP-IV）有关的疾病和病况中有用。
• WO2008/77597
  申请人：——

  公开号：——

  公开（公告）日：——
• LEDNICER D.; VOIGTLANDER P. F.; EMMERT D. E., J. MED. CHEM., 1980, 23, NO 4, 424-430
  作者：LEDNICER D.、 VOIGTLANDER P. F.、 EMMERT D. E.

  DOI：——

  日期：——
• 1-AMINOMETHYL- L- PHENYL- CYCLOHEXANE DERIVATIVES AS DDP-IV INHIBITORS
  申请人：Novartis AG

  公开号：EP2124913A1

  公开（公告）日：2009-12-02
• [EN] 1-AMINOMETHYL- L- PHENYL- CYCLOHEXANE DERIVATIVES AS DDP-IV INHIBITORS<br/>[FR] DÉRIVES DE 1-AMINOMÉTHYL- L- PHÉNYL- CYCLOHEXANE COMME INHIBITEURS DE DDP-IV
  申请人：NOVARTIS AG

  公开号：WO2008077597A1

  公开（公告）日：2008-07-03

  [EN] Compounds of the formula (I) are provided: wherein V, W, X, Y, Z, R³, R⁴, R⁵, R⁶, R⁷ and m are as defined in the specification; and pharmaceutically acceptable salts and prodrugs thereof. The compounds may be useful in the treatment or prevention of various diseases and conditions in which dipeptidylpeptidase-IV (DPP-IV) is implicated.
  [FR] L'invention concerne des composés de formule (I) : dans laquelle V, W, X, Y, Z, R³, R⁴, R⁵, R⁶, R⁷ et m sont tels que définis dans la description; ainsi que leurs sels pharmaceutiquement acceptables et leurs promédicaments. Les composés peuvent être utiles pour le traitement ou la prévention de diverses maladies et troubles dans lesquels la dipeptidylpeptidase-IV (DPP-IV) est impliquée.